202272-27-3Relevant academic research and scientific papers
Skipped Fluorination Motifs: Synthesis of Building Blocks and Comparison of Lipophilicity Trends with Vicinal and Isolated Fluorination Motifs
Troup, Robert I.,Jeffries, Benjamin,Saudain, Raphael El-Bekri,Georgiou, Eleni,Fish, Johanna,Scott, James S.,Chiarparin, Elisabetta,Fallan, Charlene,Linclau, Bruno
, p. 1882 - 1900 (2021)
Given there is an optimal lipophilicity range for orally bioavailable drugs, structural modifications applied in the drug development process are not only focused on optimizing bioactivity but also on fine-tuning lipophilicity. Fluorine introduction can b
2′-fluoronucleosides
-
Page/Page column 29; 30, (2015/11/30)
2′-Fluoro-nucleoside compounds are disclosed which are useful in the treatment of hepatitis B infection, hepatitis C infection, HIV and abnormal cellular proliferation, including tumors and cancer. The compounds have the general formulae: wherein Base is a purine or pyrimidine base;R1 is OH, H, OR3, N3, CN, halogen, CF3, lower alkyl, amino, loweralkylamino, di(lower)alkylamino, or alkoxy;R2 is H, phosphate, or a stabilized phosphate prodrug; acyl, or other pharmaceutically acceptable leaving benzyl, a lipid, an amino acid, peptide, or cholesterol; andR3 is acyl, alkyl, phosphate, or other pharmaceutically acceptable leaving group; or a pharmaceutically acceptable salt thereof.
2′-Fluoronucleosides
-
, (2008/06/13)
A class of 2′-fluoro-nucleoside compounds are disclosed which are useful in the treatment of hepatitis B infection, hepatitis C infection, HIV and abnormal cellular proliferation, including tumors and cancer. The compounds have the general formulae: wherein Base is a purine or pyrimidine base; R1is OH, H, OR3, N3, CN, halogen, including F, or CF3, lower alkyl, amino, loweralkylamino, di(lower)alkylamino, or alkoxy, and base refers to a purine or pyrimidine base; R2is H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug; acyl, or other pharmaceutically acceptable leaving group which when administered in vivo, is capable of providing a compound wherein R2is H or phosphate; sulfonate ester including alkyl or arylalkyl sulfonyl including methanesulfonyl, benzyl, wherein the phenyl group is optionally substituted with one or more substituents as described in the definition of aryl given above, a lipid, an amino acid, peptide, or cholesterol; and R3is acyl, alkyl, phosphate, or other pharmaceutically acceptable leaving group which when administered in vivo, is capable of being cleaved to the parent compound, or a pharmaceutically acceptable salt thereof.
A Completely Diastereoselective Electrophilic Fluorination of a Chiral, Noncarbohydrate Sugar Ring Precursor: Application to the Synthesis of Several Novel 2′-Fluoronucleosides
Jeffrey McAtee,Schinazi, Raymond F.,Liotta, Dennis C.
, p. 2161 - 2167 (2007/10/03)
A new and completely diastereoselective method for the introduction of fluorine into a noncarbohydrate sugar ring precursor has been developed. The use of N-fluorodibenzenesulfonimide (5) for the electrophilic fluorination of chiral lactone 4, which is derived from L-glutamic acid, yields the key intermediate 6. This is transformed into an anomeric acetate 8 and is used for the synthesis of a number of novel α-2′-fluoronucleosides. Since glutamic acid is used as the synthetic starting material, the L enantiomer may also be synthesized simply by using D-glutamic acid. The incorporation of fluorine into the 2′ position of the nucleoside provides several advantages including acid stability of the anomeric bond and general resistance to oxidative metabolism. Further, fluorine is a close mimic of hydroxyl groups in size and polarity and in its ability to act as a hydrogen bond acceptor. This may aid in the recognition of these nucleosides by the enzymes involved in nucleoside activation.
